15-67337068-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001031715.3(IQCH):c.481C>T(p.Pro161Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000616 in 1,461,372 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000062 (0 hom.)
• Consequence: IQCH NM_001031715.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.19

Genes affected

IQCH (HGNC:25721): (IQ motif containing H)

IQCH-AS1 (HGNC:44104): (IQCH antisense RNA 1)

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IQCH	NM_001031715.3	c.481C>T	p.Pro161Ser	missense_variant	5/21	ENST00000335894.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IQCH	ENST00000335894.9	c.481C>T	p.Pro161Ser	missense_variant	5/21	1	NM_001031715.3	A2
IQCH-AS1	ENST00000669759.1	n.122-46024G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000616 AC: 9 AN: 1461372 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 726990

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000720

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 27, 2022

The c.481C>T (p.P161S) alteration is located in exon 5 (coding exon 5) of the IQCH gene. This alteration results from a C to T substitution at nucleotide position 481, causing the proline (P) at amino acid position 161 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Uncertain	0.041	T
BayesDel_noAF	Benign	-0.18
Cadd	Benign	22
Dann	Uncertain	1.0
DEOGEN2	Benign	0.21	T
Eigen	Uncertain	0.38
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.034	D
MetaRNN	Uncertain	0.73	D
MetaSVM	Benign	-0.77	T
MutationAssessor	Benign	1.9	L
MutationTaster	Benign	0.99	D;D;D
PrimateAI	Benign	0.41	T
PROVEAN	Uncertain	-3.4	D
REVEL	Benign	0.23
Sift	Benign	0.14	T
Sift4G	Benign	0.20	T
Polyphen		0.95	P
Vest4		0.66
MutPred		0.53		Loss of glycosylation at T158 (P = 0.0528);
MVP		0.22
MPC		0.52
ClinPred		0.93	D
GERP RS		5.8
Varity_R		0.14
gMVP		0.31

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-67629406;